ES2244048T3 - Uso de compuestos (n)-sustituidos-1,5-didesoxi-1,5-imino-d-glucitol en terapia de combinacion para el tratamiento de infecciones con virus de hepatitis. - Google Patents

Uso de compuestos (n)-sustituidos-1,5-didesoxi-1,5-imino-d-glucitol en terapia de combinacion para el tratamiento de infecciones con virus de hepatitis.

Info

Publication number: ES2244048T3
Authority: ES; Spain
Prior art keywords: imino; glucitol; dideoxy; hepatitis; compounds
Prior art date: 1997-02-14
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Lifetime

Application number

ES98906475T

Other languages

English (en)

Spanish (es)

Inventor

Gary S. Jacob

Timothy M. Block

Raymond A. Dwek

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

GD Searle LLC

Original Assignee

GD Searle LLC

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1997-02-14

Filing date

1998-02-12

Publication date

2005-12-01

1998-02-12 Application filed by GD Searle LLC filed Critical GD Searle LLC

2005-12-01 Application granted granted Critical

2005-12-01 Publication of ES2244048T3 publication Critical patent/ES2244048T3/es

2018-02-12 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

208000006454 hepatitis Diseases 0.000 title claims abstract description 28
231100000283 hepatitis Toxicity 0.000 title claims abstract description 27
150000001875 compounds Chemical class 0.000 title claims description 63
238000011282 treatment Methods 0.000 title claims description 35
241000700605 Viruses Species 0.000 title claims description 27
208000015181 infectious disease Diseases 0.000 title claims description 25
238000002648 combination therapy Methods 0.000 title description 5
-1 N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds Chemical class 0.000 claims abstract description 31
239000000203 mixture Substances 0.000 claims abstract description 25
239000003814 drug Substances 0.000 claims description 30
230000000840 anti-viral effect Effects 0.000 claims description 21
NNGHJVIFXDFMGO-GKROBHDKSA-N [[(2r,3s,5r)-5-(4-amino-2-oxopyrimidin-1-yl)-3-sulfanyloxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](S)C1 NNGHJVIFXDFMGO-GKROBHDKSA-N 0.000 claims description 17
239000008194 pharmaceutical composition Substances 0.000 claims description 15
FTSCEGKYKXESFF-LXTVHRRPSA-N N-nonyldeoxynojirimycin Chemical compound CCCCCCCCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO FTSCEGKYKXESFF-LXTVHRRPSA-N 0.000 claims description 13
238000002360 preparation method Methods 0.000 claims description 11
206010019799 Hepatitis viral Diseases 0.000 claims description 8
125000000217 alkyl group Chemical group 0.000 claims description 5
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 2
125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
239000002777 nucleoside Substances 0.000 abstract description 25
150000003833 nucleoside derivatives Chemical class 0.000 abstract description 19
239000003443 antiviral agent Substances 0.000 abstract description 15
238000000034 method Methods 0.000 abstract description 15
239000003795 chemical substances by application Substances 0.000 abstract description 11
239000002773 nucleotide Substances 0.000 abstract description 11
125000003729 nucleotide group Chemical group 0.000 abstract description 11
241000124008 Mammalia Species 0.000 abstract description 8
230000009385 viral infection Effects 0.000 abstract description 8
239000002955 immunomodulating agent Substances 0.000 abstract description 5
229940121357 antivirals Drugs 0.000 abstract description 3
230000002519 immonomodulatory effect Effects 0.000 abstract description 3
239000003022 immunostimulating agent Substances 0.000 abstract 2
241001465754 Metazoa Species 0.000 description 27
229940079593 drug Drugs 0.000 description 27
230000000694 effects Effects 0.000 description 22
241000700721 Hepatitis B virus Species 0.000 description 21
208000002672 hepatitis B Diseases 0.000 description 20
108020004414 DNA Proteins 0.000 description 18
150000003839 salts Chemical class 0.000 description 11
210000004027 cell Anatomy 0.000 description 10
238000009472 formulation Methods 0.000 description 9
230000036470 plasma concentration Effects 0.000 description 9
241000283923 Marmota monax Species 0.000 description 8
241000555745 Sciuridae Species 0.000 description 8
210000002966 serum Anatomy 0.000 description 8
230000002155 anti-virotic effect Effects 0.000 description 7
230000005764 inhibitory process Effects 0.000 description 7
125000003835 nucleoside group Chemical group 0.000 description 7
238000012360 testing method Methods 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
238000004458 analytical method Methods 0.000 description 6
238000013459 approach Methods 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
239000000243 solution Substances 0.000 description 6
239000000725 suspension Substances 0.000 description 6
238000002560 therapeutic procedure Methods 0.000 description 6
241000282412 Homo Species 0.000 description 5
230000004044 response Effects 0.000 description 5
239000003826 tablet Substances 0.000 description 5
208000000419 Chronic Hepatitis B Diseases 0.000 description 4
108020005202 Viral DNA Proteins 0.000 description 4
239000002253 acid Substances 0.000 description 4
239000002671 adjuvant Substances 0.000 description 4
239000000427 antigen Substances 0.000 description 4
102000036639 antigens Human genes 0.000 description 4
108091007433 antigens Proteins 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
208000019425 cirrhosis of liver Diseases 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
230000002401 inhibitory effect Effects 0.000 description 4
230000004048 modification Effects 0.000 description 4
238000012986 modification Methods 0.000 description 4
239000003921 oil Substances 0.000 description 4
235000019198 oils Nutrition 0.000 description 4
229920001223 polyethylene glycol Polymers 0.000 description 4
239000002904 solvent Substances 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
201000001862 viral hepatitis Diseases 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
LXBIFEVIBLOUGU-UHFFFAOYSA-N Deoxymannojirimycin Natural products OCC1NCC(O)C(O)C1O LXBIFEVIBLOUGU-UHFFFAOYSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
101710142246 External core antigen Proteins 0.000 description 3
206010016654 Fibrosis Diseases 0.000 description 3
241000725303 Human immunodeficiency virus Species 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
239000002775 capsule Substances 0.000 description 3
230000007882 cirrhosis Effects 0.000 description 3
238000011161 development Methods 0.000 description 3
201000010099 disease Diseases 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
239000000890 drug combination Substances 0.000 description 3
LXBIFEVIBLOUGU-JGWLITMVSA-N duvoglustat Chemical compound OC[C@H]1NC[C@H](O)[C@@H](O)[C@@H]1O LXBIFEVIBLOUGU-JGWLITMVSA-N 0.000 description 3
239000007788 liquid Substances 0.000 description 3
239000006187 pill Substances 0.000 description 3
239000000843 powder Substances 0.000 description 3
239000000047 product Substances 0.000 description 3
230000009467 reduction Effects 0.000 description 3
230000028327 secretion Effects 0.000 description 3
230000009466 transformation Effects 0.000 description 3
230000032258 transport Effects 0.000 description 3
PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
ZZKNRXZVGOYGJT-VKHMYHEASA-N (2s)-2-[(2-phosphonoacetyl)amino]butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)CP(O)(O)=O ZZKNRXZVGOYGJT-VKHMYHEASA-N 0.000 description 2
ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
238000002965 ELISA Methods 0.000 description 2
108010056771 Glucosidases Proteins 0.000 description 2
102000004366 Glucosidases Human genes 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
238000010222 PCR analysis Methods 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
208000036142 Viral infection Diseases 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
239000008280 blood Substances 0.000 description 2
150000001649 bromium compounds Chemical class 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
230000008859 change Effects 0.000 description 2
238000002512 chemotherapy Methods 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
230000003247 decreasing effect Effects 0.000 description 2
235000005911 diet Nutrition 0.000 description 2
230000037213 diet Effects 0.000 description 2
235000014113 dietary fatty acids Nutrition 0.000 description 2
230000008034 disappearance Effects 0.000 description 2
231100000676 disease causative agent Toxicity 0.000 description 2
231100000673 dose–response relationship Toxicity 0.000 description 2
238000000921 elemental analysis Methods 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
239000000194 fatty acid Substances 0.000 description 2
229930195729 fatty acid Natural products 0.000 description 2
150000004665 fatty acids Chemical class 0.000 description 2
239000008187 granular material Substances 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
238000009396 hybridization Methods 0.000 description 2
229940121354 immunomodulator Drugs 0.000 description 2
238000002329 infrared spectrum Methods 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
150000004694 iodide salts Chemical class 0.000 description 2
JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 2
208000019423 liver disease Diseases 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
239000000463 material Substances 0.000 description 2
238000005259 measurement Methods 0.000 description 2
239000002609 medium Substances 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
239000002245 particle Substances 0.000 description 2
230000002085 persistent effect Effects 0.000 description 2
239000000651 prodrug Substances 0.000 description 2
229940002612 prodrug Drugs 0.000 description 2
238000003753 real-time PCR Methods 0.000 description 2
230000010076 replication Effects 0.000 description 2
238000011160 research Methods 0.000 description 2
238000012552 review Methods 0.000 description 2
238000013207 serial dilution Methods 0.000 description 2
238000009097 single-agent therapy Methods 0.000 description 2
239000000375 suspending agent Substances 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
231100000419 toxicity Toxicity 0.000 description 2
230000001988 toxicity Effects 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
238000011269 treatment regimen Methods 0.000 description 2
229960005486 vaccine Drugs 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
230000029812 viral genome replication Effects 0.000 description 2
210000002845 virion Anatomy 0.000 description 2
230000003612 virological effect Effects 0.000 description 2
230000003442 weekly effect Effects 0.000 description 2
229960002555 zidovudine Drugs 0.000 description 2
HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 2
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical class CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical class CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical class BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
XEDONBRPTABQFB-UHFFFAOYSA-N 4-[(2-formyl-3-hydroxyphenoxy)methyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1COC1=CC=CC(O)=C1C=O XEDONBRPTABQFB-UHFFFAOYSA-N 0.000 description 1
YLDCUKJMEKGGFI-QCSRICIXSA-N 4-acetamidobenzoic acid;9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purin-6-one;1-(dimethylamino)propan-2-ol Chemical compound CC(O)CN(C)C.CC(O)CN(C)C.CC(O)CN(C)C.CC(=O)NC1=CC=C(C(O)=O)C=C1.CC(=O)NC1=CC=C(C(O)=O)C=C1.CC(=O)NC1=CC=C(C(O)=O)C=C1.O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(NC=NC2=O)=C2N=C1 YLDCUKJMEKGGFI-QCSRICIXSA-N 0.000 description 1
FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
208000030507 AIDS Diseases 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
229920000936 Agarose Polymers 0.000 description 1
229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
208000009594 Animal Hepatitis Diseases 0.000 description 1
241000272517 Anseriformes Species 0.000 description 1
101000959414 Bacillus thermoamyloliquefaciens Alpha-glucosidase 2 Proteins 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
VWFCHDSQECPREK-LURJTMIESA-N Cidofovir Chemical compound NC=1C=CN(C[C@@H](CO)OCP(O)(O)=O)C(=O)N=1 VWFCHDSQECPREK-LURJTMIESA-N 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
241000450599 DNA viruses Species 0.000 description 1
108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
206010059866 Drug resistance Diseases 0.000 description 1
101710091045 Envelope protein Proteins 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
229940126656 GS-4224 Drugs 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
102000000340 Glucosyltransferases Human genes 0.000 description 1
108010055629 Glucosyltransferases Proteins 0.000 description 1
229930186217 Glycolipid Natural products 0.000 description 1
102000003886 Glycoproteins Human genes 0.000 description 1
108090000288 Glycoproteins Proteins 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
206010019663 Hepatic failure Diseases 0.000 description 1
208000005176 Hepatitis C Diseases 0.000 description 1
208000005331 Hepatitis D Diseases 0.000 description 1
206010019771 Hepatitis F Diseases 0.000 description 1
206010019773 Hepatitis G Diseases 0.000 description 1
208000037262 Hepatitis delta Diseases 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
102100034349 Integrase Human genes 0.000 description 1
102000006992 Interferon-alpha Human genes 0.000 description 1
108010047761 Interferon-alpha Proteins 0.000 description 1
102000014150 Interferons Human genes 0.000 description 1
108010050904 Interferons Proteins 0.000 description 1
YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
HLFSDGLLUJUHTE-SNVBAGLBSA-N Levamisole Chemical compound C1([C@H]2CN3CCSC3=N2)=CC=CC=C1 HLFSDGLLUJUHTE-SNVBAGLBSA-N 0.000 description 1
241000701076 Macacine alphaherpesvirus 1 Species 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
239000005642 Oleic acid Substances 0.000 description 1
ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
239000004372 Polyvinyl alcohol Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
101710188315 Protein X Proteins 0.000 description 1
239000012980 RPMI-1640 medium Substances 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
101000874347 Streptococcus agalactiae IgA FC receptor Proteins 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
244000299461 Theobroma cacao Species 0.000 description 1
235000009470 Theobroma cacao Nutrition 0.000 description 1
ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
108010067390 Viral Proteins Proteins 0.000 description 1
108020000999 Viral RNA Proteins 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
MJOQJPYNENPSSS-XQHKEYJVSA-N [(3r,4s,5r,6s)-4,5,6-triacetyloxyoxan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1CO[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O MJOQJPYNENPSSS-XQHKEYJVSA-N 0.000 description 1
QMHAHUAQAJVBIW-UHFFFAOYSA-N [methyl(sulfamoyl)amino]methane Chemical compound CN(C)S(N)(=O)=O QMHAHUAQAJVBIW-UHFFFAOYSA-N 0.000 description 1
239000000205 acacia gum Substances 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
230000009471 action Effects 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
239000000654 additive Substances 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
238000012382 advanced drug delivery Methods 0.000 description 1
238000000246 agarose gel electrophoresis Methods 0.000 description 1
229940072056 alginate Drugs 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
229920013820 alkyl cellulose Chemical class 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
230000004075 alteration Effects 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
238000010171 animal model Methods 0.000 description 1
239000003472 antidiabetic agent Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
229940009098 aspartate Drugs 0.000 description 1
238000003556 assay Methods 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
150000007514 bases Chemical class 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
230000008901 benefit Effects 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
229940050390 benzoate Drugs 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
239000000872 buffer Substances 0.000 description 1
235000014121 butter Nutrition 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
210000000234 capsid Anatomy 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
238000007385 chemical modification Methods 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
229940001468 citrate Drugs 0.000 description 1
230000002301 combined effect Effects 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
229940104302 cytosine Drugs 0.000 description 1
238000013461 design Methods 0.000 description 1
239000003599 detergent Substances 0.000 description 1
150000008050 dialkyl sulfates Chemical class 0.000 description 1
DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical class CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
229910001873 dinitrogen Inorganic materials 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
229940043264 dodecyl sulfate Drugs 0.000 description 1
241001493065 dsRNA viruses Species 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
238000009505 enteric coating Methods 0.000 description 1
229940072253 epivir Drugs 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
239000012091 fetal bovine serum Substances 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
230000037406 food intake Effects 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
239000012634 fragment Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000008103 glucose Substances 0.000 description 1
150000002303 glucose derivatives Chemical class 0.000 description 1
108010050669 glucosidase I Proteins 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
208000005252 hepatitis A Diseases 0.000 description 1
208000029570 hepatitis D virus infection Diseases 0.000 description 1
201000010284 hepatitis E Diseases 0.000 description 1
MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
230000006872 improvement Effects 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
238000001802 infusion Methods 0.000 description 1
238000011221 initial treatment Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
230000002452 interceptive effect Effects 0.000 description 1
229940079322 interferon Drugs 0.000 description 1
229950000038 interferon alfa Drugs 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
238000002955 isolation Methods 0.000 description 1
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
229960003299 ketamine Drugs 0.000 description 1
239000008101 lactose Substances 0.000 description 1
229960001627 lamivudine Drugs 0.000 description 1
229960001614 levamisole Drugs 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
201000007270 liver cancer Diseases 0.000 description 1
208000007903 liver failure Diseases 0.000 description 1
231100000835 liver failure Toxicity 0.000 description 1
208000014018 liver neoplasm Diseases 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
239000000395 magnesium oxide Substances 0.000 description 1
CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
210000004962 mammalian cell Anatomy 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
UQRORFVVSGFNRO-UTINFBMNSA-N miglustat Chemical compound CCCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO UQRORFVVSGFNRO-UTINFBMNSA-N 0.000 description 1
238000002156 mixing Methods 0.000 description 1
125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
239000011664 nicotinic acid Substances 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
231100000344 non-irritating Toxicity 0.000 description 1
239000000346 nonvolatile oil Substances 0.000 description 1
229940127073 nucleoside analogue Drugs 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
229920001542 oligosaccharide Polymers 0.000 description 1
150000002482 oligosaccharides Chemical class 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000006179 pH buffering agent Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
230000000149 penetrating effect Effects 0.000 description 1
239000002304 perfume Substances 0.000 description 1
JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
229940075930 picrate Drugs 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
229950010765 pivalate Drugs 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
239000000902 placebo Substances 0.000 description 1
229940068196 placebo Drugs 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
230000008569 process Effects 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000004853 protein function Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
231100000916 relative toxicity Toxicity 0.000 description 1
230000017610 release of virus from host Effects 0.000 description 1
239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical class OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
230000000405 serological effect Effects 0.000 description 1
238000009589 serological test Methods 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
235000002639 sodium chloride Nutrition 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
229960002920 sorbitol Drugs 0.000 description 1
241000894007 species Species 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
150000003431 steroids Chemical class 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000002992 thymic effect Effects 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000002110 toxicologic effect Effects 0.000 description 1
231100000027 toxicology Toxicity 0.000 description 1
150000003626 triacylglycerols Chemical class 0.000 description 1
229950009795 tucaresol Drugs 0.000 description 1
ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
241001430294 unidentified retrovirus Species 0.000 description 1
HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
230000006490 viral transcription Effects 0.000 description 1
229960000523 zalcitabine Drugs 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Chemical & Material Sciences (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Medicinal Chemistry (AREA)
Epidemiology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Virology (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Gastroenterology & Hepatology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Molecular Biology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

ES98906475T 1997-02-14 1998-02-12 Uso de compuestos (n)-sustituidos-1,5-didesoxi-1,5-imino-d-glucitol en terapia de combinacion para el tratamiento de infecciones con virus de hepatitis. Expired - Lifetime ES2244048T3 (es)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US4122197P	1997-02-14	1997-02-14
US41221P		1997-02-14

Publications (1)

Publication Number	Publication Date
ES2244048T3 true ES2244048T3 (es)	2005-12-01

Family

ID=21915395

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ES98906475T Expired - Lifetime ES2244048T3 (es)	1997-02-14	1998-02-12	Uso de compuestos (n)-sustituidos-1,5-didesoxi-1,5-imino-d-glucitol en terapia de combinacion para el tratamiento de infecciones con virus de hepatitis.

Country Status (8)

Country	Link
EP (1)	EP1007058B1 (de)
JP (1)	JP2001512462A (de)
CN (1)	CN100382804C (de)
AT (1)	ATE295732T1 (de)
AU (1)	AU6169298A (de)
DE (1)	DE69830241T2 (de)
ES (1)	ES2244048T3 (de)
WO (1)	WO1998035685A1 (de)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20030100532A1 (en)	1997-02-14	2003-05-29	Gary S. Jacob	Use of n-substituted-1,5-dideoxy-1,5-imino-d-glucitol compounds in combination therapy for treating hepatitis virus infections
ZA9810210B (en)	1997-11-10	1999-07-14	Searle & Co	Use of alkylated iminosugars to treat multidrug resistance.
US6465488B1 (en)	1997-12-11	2002-10-15	Chancellor, Masters & Scholars Of The University Of Oxford	Inhibition of glycolipid biosynthesis
AU761748B2 (en) *	1997-12-11	2003-06-12	Chancellor, Masters And Scholars Of The University Of Oxford, The	Inhibition of membrane-associated viral replication
US6689759B1 (en)	1998-02-12	2004-02-10	G. D. Searle & Co.	Methods of Treating hepatitis virus infections with N-substituted-1,5-dideoxy-1,5-imino-d-glucitol compounds in combination therapy
ATE331515T1 (de) *	1998-02-12	2006-07-15	Searle Llc	Verwendung von n-substituirten-1,5-dideoxy-1,5- imino-d-glucitolen zur behandlung von hepatitis infektionen
EP1714676A3 (de) *	1998-02-12	2006-11-15	G.D. Searle LLC.	N-substituierte 1,5-dideoxy-1,5-imino-D-glucitol Verbindungen für die Therapie von Hepatitis Virus Infektionen
ES2311921T3 (es)	1999-02-12	2009-02-16	United Therapeutics Corporation	N-(8,8,8-trifluorooctil)1-5,-didesoxi-1,5-imino-d-glucitol para tratar infecciones por el virus de la hepatitis.
AU3858600A (en) *	1999-02-12	2001-02-19	G.D. Searle & Co.	Glucamine compounds for treating hepatitis virus infections
EP1658846B1 (de) *	1999-02-12	2008-07-30	United Therapeutics Corporation	N-(8,8,8-Trifluorooctyl)-1,5-dideoxy-1,5-imino-D-glucitol zur Behandlung von Hepatitis-Virus-Infektionen
US7256005B2 (en)	1999-08-10	2007-08-14	The Chancellor, Masters And Scholars Of The University Of Oxford	Methods for identifying iminosugar derivatives that inhibit HCV p7 ion channel activity
HK1046869A1 (zh) *	1999-08-10	2003-01-30	The Chancellor, Masters And Scholars Of The University Of Oxford	使用长链n烷基化合物及其恶衍生物作为抗病毒成分
CN1422156A (zh) *	2000-02-14	2003-06-04	法马西亚公司	N－取代的－1,5－二脱氧－1,5－亚氨基－d－葡萄糖醇化合物在治疗肝炎病毒感染中的用途
JP2006515577A (ja) *	2002-09-23	2006-06-01	ザ・チャンセラー，マスターズ・アンド・スカラーズ・オヴ・ザ・ユニヴァーシティ・オヴ・オックスフォード	イオンチャネル活性を阻害するためのイミノ糖誘導体の使用
WO2020053654A1 (en)	2018-09-12	2020-03-19	Novartis Ag	Antiviral pyridopyrazinedione compounds
CN114667285B (zh)	2019-09-26	2025-08-08	诺华股份有限公司	抗病毒吡唑并吡啶酮化合物

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU7518694A (en) *	1993-08-20	1995-03-21	G.D. Searle & Co.	Retroviral protease inhibitors and combinations thereof

1998
- 1998-02-12 AU AU61692/98A patent/AU6169298A/en not_active Abandoned
- 1998-02-12 EP EP98906475A patent/EP1007058B1/de not_active Expired - Lifetime
- 1998-02-12 WO PCT/US1998/003004 patent/WO1998035685A1/en not_active Ceased
- 1998-02-12 DE DE69830241T patent/DE69830241T2/de not_active Expired - Lifetime
- 1998-02-12 AT AT98906475T patent/ATE295732T1/de not_active IP Right Cessation
- 1998-02-12 CN CNB988039427A patent/CN100382804C/zh not_active Expired - Fee Related
- 1998-02-12 JP JP53598798A patent/JP2001512462A/ja active Pending
- 1998-02-12 ES ES98906475T patent/ES2244048T3/es not_active Expired - Lifetime

Also Published As

Publication number	Publication date
DE69830241T2 (de)	2006-01-26
EP1007058B1 (de)	2005-05-18
ATE295732T1 (de)	2005-06-15
CN100382804C (zh)	2008-04-23
AU6169298A (en)	1998-09-08
JP2001512462A (ja)	2001-08-21
CN1251993A (zh)	2000-05-03
EP1007058A1 (de)	2000-06-14
DE69830241D1 (de)	2005-06-23
HK1027509A1 (en)	2001-01-19
WO1998035685A1 (en)	1998-08-20

Publication	Publication Date	Title
ES2272054T3 (es)	2007-04-16	Uso de compuestos de n-sustituido-1,5-didesoxi-1,5-imino-d-glucitol para tratar infecciones por el virus de la hepatitis.
ES2244048T3 (es)	2005-12-01	Uso de compuestos (n)-sustituidos-1,5-didesoxi-1,5-imino-d-glucitol en terapia de combinacion para el tratamiento de infecciones con virus de hepatitis.
ES2649410T3 (es)	2018-01-11	Agentes antivirales para la hepatitis B
US7816560B1 (en)	2010-10-19	Long chain n-alkyl compounds and oxa-derivatives thereof
US6689759B1 (en)	2004-02-10	Methods of Treating hepatitis virus infections with N-substituted-1,5-dideoxy-1,5-imino-d-glucitol compounds in combination therapy
ES2311921T3 (es)	2009-02-16	N-(8,8,8-trifluorooctil)1-5,-didesoxi-1,5-imino-d-glucitol para tratar infecciones por el virus de la hepatitis.
US20110171174A1 (en)	2011-07-14	Synergistic Combinations of a Macrocyclic Inhibitor of HCV and a Nucleoside
BR112021000938A2 (pt)	2021-04-27	composto sal farmaceuticamente aceitável, tautômero, isômero ou estereoisômero do mesmo, composição farmacêutica e processo para a síntese do dito composto
ES2325088T3 (es)	2009-08-25	Compuestos utiles en el tratamiento de hiv.
US20050119310A1 (en)	2005-06-02	Use of n-substituted-1,5-dideoxy-1,5-imino-d-glucitol compounds for treating hepatitis virus infections
US7612093B2 (en)	2009-11-03	Compositions of treating hepatitis virus infections with N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds in combination therapy
PT1382343E (pt)	2010-03-10	Terapia de combinação para tratamento do vírus da hepatite b
JP4887305B2 (ja)	2012-02-29	Ｈｉｖの治療に有用な化合物
JP2008526713A5 (de)	2009-04-09
CA2167841A1 (en)	1995-02-02	Method of inhibiting the production of human immunodeficiency viruses with substituted azaspiranes
EP1714676A2 (de)	2006-10-25	N-substituierte 1,5-dideoxy-1,5-imino-D-glucitol Verbindungen für die Therapie von Hepatitis Virus Infektionen
HK1027509B (en)	2008-10-31	Use of n-substituted-1,5-dideoxy-1,5-imino-d-glucitol compounds in manueacturing a medicament for treating hepatitis virus infections
WO2010151672A2 (en)	2010-12-29	Amino acid derived ureas